Generic name: roxadustat
Companies: FibroGen, AstraZeneca and Astellas
Disease: anemia due to chronic kidney disease
2024 sales estimate: $1.88 billion
China was the first country to approve roxadustat, a first-in-class oral treatment designed to treat patients with anemia caused by chronic kidney disease. Because of a manufacturing shift, the drug won’t launch until the second half of 2019, but when it does, Leerink analyst Geoffrey Porges has projected sales of about $1 billion in China alone by 2025.
Roxadustat is the first hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) to land an approval. It works by restoring production of the hormone erythropoietin and improving iron regulation, both key to blood cell production.
In a phase 3 study on Chinese dialysis-dependent patients, the drug matched up to Johnson & Johnson and Amgen’s standard therapy Epogen/Procrit at increasing hemoglobin levels after 26 weeks. The erythropoiesis-stimulating agent (ESA) is sold in China by Kyowa Kirin.
The noninferiority data are only part of roxadustat’s competitive picture. First, it's an oral treatment given three times weekly, whereas ESAs are injected intravenously or under the skin. HIF-PHIs like roxadustat also increase the availability of iron, while ESAs only stimulate erythropoietin. Some ESA patients need to take iron supplements and undertake regular iron level checks.
But as Porges sees it, the main upside for roxadustat lies in its cardiovascular safety profile. Back in the 2000s, evidence started to emerge linking ESAs with higher risks of CV events and tumor growth. FDA black-box warnings on the entire class followed, advising physicians to use more conservative dosing.
Industry watchers initially believed roxadustat could do much better in terms of CV safety, but wording in a statement on a pooled analysis of roxadustat's CV profile confused some. Without giving any specific numbers for major adverse cardiovascular events, the company said the drug only showed “no clinically meaningful difference” compared to placebo in the non-dialysis-dependent setting or to ESA in dialysis-dependent patients.
But after talking to management to unpack “a very complex dataset,” analysts at Jefferies said the readout is better than investors had feared and ultimately a positive for FibroGen and its partners.
Roxadustat’s Chinese approval could soon expand into the much larger non-dialysis-dependent population on the back of positive phase 3 results. And U.S. and European filings are expected this year, followed by launches in 2020. AstraZeneca collaborates with FibroGen, the drug's original developer, in the U.S. and China, while Astellas helps in Japan and Europe.